Biomaterials as Stem Cell Niche (eBook)

Preface 5
Contents 7
Engineering ECM Complexity into Biomaterials for Directing Cell Fate 9
Abstract 9
1. Cell--ECM Interactions 9
1.1 ECM Composition and Signaling 10
1.2 ECM Regulation 11
1.2.1 Proteolytic Processing of the ECM 11
1.2.2 Mechanochemical Translation of Cell-binding ECM Domains 13
2. ECM and the Stem Cell Niche 16
2.1 Integrins: A Sign of ‘‘Stemness’’ 16
2.2 Neural Stem Cells and Integrin/ECM Alterations 17
2.2.1 Integrin and ECM Profile During Neural Development 17
2.2.2 ECM and Integrin Profile in Adult Neural Stem Cell Niche 18
2.2.3 Functional Role of ECM/Integrin Interactions 19
3. Current Biomaterials Approaches 20
3.1 Biomimetic Approaches 20
3.2 Engineering Protein Variants 21
3.3 Future Directions for Biomaterials as Stem Cell Niches 22
References 23
Functional Biomaterials for Controlling Stem Cell Differentiation 27
Abstract 27
1. Introduction 28
1.1 Emergence of Stem Cell Engineering in Regenerative Medicine 28
1.2 Stem Cell Sources 28
2. Stem Cell Expansion and Differentiation Using Biomaterials 29
2.1 Roles of ECM in Stem Cell Differentiation 29
2.2 Mimicking ECM with Synthetic Biomaterials 30
2.2.1 Mimicking the Biophysical and Biochemical Properties of ECM 30
Functionalization of Synthetic Substrates with ECM Derived Ligands 31
2.2.2 Effects of the Cell--Matrix Interface 31
Surface Chemistry and Interfacial Energy 31
2.2.3 Mineralization of Matrix Materials 37
Mineralization of Polymeric Matrices 38
Effect of Mineralization on Cell Adhesion, Proliferation and Differentiation 38
2.2.4 Mechanical Properties 40
2.3 Biomaterial Based Delivery of Soluble Factors for 3D Cell Culture 40
2.3.1 Incorporation of Bioactive Agents into Matrix Materials 40
2.3.2 Effects of Controlled Delivery of Bioactive Agents on Stem Cell Differentiation 42
Delivery of Bioactive Agents to Embryonic Stem Cells 42
Tissue Specific Differentiation of Stem Cells Using Delivery of Bioactive Agents 44
2.4 In Vivo Applications 45
2.5 Future Perspectives 46
Acknowledgments 47
References 47
Integration of Biomaterials into 3D Stem Cell Microenvironments 53
Abstract 53
1. Introduction 53
1.1 Culture in Two or Three Dimensions 55
1.2 Strategies for Biomaterial Control of the 3D Microenvironment 55
2. Scaffolds 56
3. Encapsulation 59
4. Microcarriers and Microparticles 60
4.1 Microcarriers 61
4.2 Microparticles 61
5. Summary and Conclusions 63
References 63
Stem Cell Interaction with Topography 68
Abstract 68
1. Introduction 68
1.1 Extracellular Topography 69
1.2 Nanotopography 70
2. Nanofabrication Techniques 71
3. Stem Cells Reception to Topography 75
3.1 Embryonic Stem Cells 75
3.2 Neural Progenitor Cells/Neural Stem Cells 77
3.3 Mesenchymal Stem Cells 78
4. Making Sense of Physical Cues in the Extracellular Matrix: Mechanotransduction 81
4.1 Introduction to the ECM 81
4.2 Mechanotransduction: A Direct Connection? 82
4.3 Connecting with the ECM: Cell--Matrix Interactions 82
4.4 Integrins and Focal Adhesions: Inside Out and Outside In 84
4.5 Cytoskeleton: Force Transmission 85
4.5.1 Cell Exerting Forces on the Underlying Substrate 85
4.6 Filopodia: Probing the ECM 86
4.7 Nucleus: Gene Regulation 87
5. Conclusion 87
References 88
The Nanofiber Matrix as an Artificial Stem Cell Niche 95
Abstract 95
1. The Stem Cell Niche 95
2. Nanoscale Topography in the Extracellular Matrix 97
3. Methods to Generate Nanofibrous Matrices 98
3.1 Electrospinning 98
3.2 Self-assembly 100
3.3 Solution Phase Separation 102
3.4 Comparison of Nanofiber Generation Methods 104
4. Nanofibrous Matrices for Stem Cell Expansion 105
4.1 Nanofiber-mediated Expansion of Human Hematopoietic Stem Cells (HSCs) 105
4.2 Nanofiber-mediated Expansion of Neural Stem Cells (NSCs) 108
4.3 Nanofiber-mediated Expansion of Embryonic Stem Cells (ESCs) 108
4.4 Nanofiber-mediated Expansion of Mesenchymal Stem Cells (MSCs) 109
5. Nanofiber Matrices for Differentiation of Stem Cells 109
5.1 Nanofiber-mediated Stem Cell Differentiation into Neuronal Lineages 110
5.2 Nanofiber-mediated Stem Cell Differentiation into Chondrogenic and Osteogenic Lineages 112
5.3 Nanofiber-mediated Stem Cell Differentiation into Myogenic Lineage 114
6. Nanofibrous Matrices for Stem Cell Delivery 115
7. Summary 117
References 118
Micropatterned Hydrogels for Stem Cell Culture 125
Abstract 125
1. Introduction: Application of Biomaterial Technologies to Stem Cell Research 126
2. Stem Cells 128
2.1 MSC General Characteristics 128
2.2 MSC Differentiation and Plasticity 129
3. Hydrogels 130
3.1 Natural Versus Synthetic Polymers 131
3.2 Gelation Mechanisms 131
3.2.1 Radical Chain Polymerization 132
3.2.2 Chemical Cross-linking 132
3.3 Functionalization of Hydrogels 132
3.3.1 Biodegradable Hydrogels 132
3.3.2 Biomimetic hydrogels 133
4. Micropatterning 133
4.1 Microfabrication Technology 134
4.2 Applications in Hydrogel Patterning 135
4.2.1 Photolithography 135
4.2.2 Laser-scanning lithography 136
4.2.3 Stop-flow Lithography 137
4.2.4 Optofluidic Maskless Lithography 138
4.2.5 Photodegradation 139
4.2.6 Micromolding 140
4.2.7 Two-dimensional Templating 141
5. Micropatterning Hydrogels with Embedded Cells 141
5.1 Culture of One Cell Type 142
5.1.1 Cell Viability 142
5.1.2 Cell Migration (and Morphology) 143
5.1.3 Cell Differentiation 145
5.2 Culture of Multiple Cell Types 145
5.2.1 Microfluidics 145
5.2.2 Bioreactors 147
5.2.3 Micromolding 147
5.2.4 Stop-flow Lithography 148
6…Future Outlook 148
References 149
Microengineering Approach for Directing Embryonic Stem Cell Differentiation 159
Abstract 159
1. Introduction 159
2. Control of the Cellular Microenvironment 161
2.1 Cell--cell Contacts 161
2.2 Cell--soluble Factor Interactions 162
2.3 Cell--extracellular Matrix Interactions 163
3. Microengineering the Environment 164
3.1 Microfluidic Platforms for Controlling Cell--soluble Factor Interactions 165
3.2 Controlled Microbioreactors 166
3.3 Surface Micropatterning for Controlling Cell--cell Contacts 167
3.4 High-throughput Microarrays for Screening Microenvironments 169
3.5 Three Dimensional Scaffolds for Culturing ESCs 170
3.6 Tissue Engineering Using Assembly of Microengineered Building Blocks 170
4. Conclusions 172
References 173
Biomaterials as Stem Cell Niche: Cardiovascular Stem Cells 178
Abstract 178
1. Introduction 179
2. Adult Cardiovascular Stem Cells and Their Niches 179
2.1 Cardiac Stem Cells 179
2.2 Endothelial Progenitor Cells 181
2.3 Mural Cell Progenitors/Mesenchymal Stem Cells 182
2.4 Adult Cardiovascular Stem Cell Niches 183
3. Biomaterials as Stem Cell Niches for 3D Cell Culture 184
3.1 3D Cell Culture Systems for Pluripotent Stem Cells 184
3.2 3D Cell Culture Systems for Adult Stem Cells 187
4. Biomaterials as Stem Cell Niches for Cardiac Cell Therapy 189
4.1 Cardiac Cell Therapy 189
4.2 Biomaterial Scaffolds for Cardiac Cell Therapy 190
5. Conclusions 192
References 193
The Integrated Role of Biomaterials and Stem Cells in Vascular Regeneration 199
Abstract 199
1. Introduction 200
2. Stem Cells for Vascular Regeneration 201
2.1 Vascular Development of ECs and SMCs from Pluripotent Stem Cells 201
2.2 Stem-cell-derived Vascular Cells 203
2.2.1 Stem-cell-derived ECs 203
Endothelial Progenitor Cells 205
ECs Derived from ESC and iPSC Populations 206
2.2.2 Stem-cell-derived SMCs 207
3. Biomimetic Scaffolds for Vascular Regeneration 208
3.1 General Requirements for Biomimetic Scaffolds 208
3.2 Polymeric Biomimetic Scaffolds 209
3.3 Scaffold Types 213
3.3.1 Hydrogels 213
3.3.2 Electrospun Fibers 213
3.3.3 Other Scaffolds 214
3.4 Vascular Engineering Scaffold Properties 214
3.4.1 Degradation Properties 214
3.4.2 Substrate Topography 215
3.4.3 Mechanical Stimulation 215
4. Inclusion of Vascular Stem and Somatic Cells into Biomaterials 216
4.1 Biomaterials to Engineer Blood Vessels 216
4.2 Biomaterials to Deliver Cells to Host Vasculature 217
4.3 Biomaterials to Induce Differentiation 217
5. Future Perspectives 218
6…Conclusion 219
References 219
Synthetic Niches for Stem Cell Differentiation into T cells 228
Abstract 228
1. Introduction 229
2. The T Cell Niche 230
2.1 T Cell Receptor Gene Rearrangement 232
2.2 T Cell Microenvironment 232
3. T Cell Differentiation Through Co-culture 234
4. T Cell Differentiation Through Immobilization of Notch Ligands 237
4.1 T Cell Differentiation Through Plate Immobilization 238
4.2 T Cell Differentiation Through Notch--Ligand Presenting Microbeads 240
5. Generation of Antigen-specific T Cells from Stem Cells 240
5.1 Retroviral Transduction of T Cell Receptors 241
5.2 T Cell Differentiation in a Three-dimensional Matrix 243
Acknowledgments 245
References 246
Understanding Hypoxic Environments: Biomaterials Approaches to Neural Stabilization and Regeneration after Ischemia 249
Abstract 249
1. Ischemic Brain Damage in Adult and Neonatal Humans 250
2. Response of NSPCs to Ischemic Brain Damage 250
3. NSPC Implants to Treat Ischemic Brain Damage 252
4. NSPC Isolation and Culture: State-of-the-Art 253
5. Biomaterials Use in NSPC Applications: State-of-the-Art 255
6. Current Challenges in Biomaterials for NSPC Applications 258
7. Potential of Biomaterials for Reverse-engineering NSPC Microenvironments 259
7.1 Neurosphere Culture 259
7.2 The Stem Cell Niche 260
7.3 ‘‘Physiological Hypoxia’’ and Hypoxic/Ischemic Injury 261
8. Conclusions 264
Acknowledgments 265
References 265
Biomaterial Applications in the Adult Skeletal Muscle Satellite Cell Niche: Deliberate Control of Muscle Stem Cells and Muscle Regeneration in the Aged Niche 277
Abstract 277
1. Introduction 278
2. Skeletal Muscle is Regenerated and Maintained by Muscle Stem Cells 280
2.1 Delta/Notch Signaling Leads to Activation and Proliferation of Satellite Cells 280
2.2 Wnt Signaling Cues Myogenic Progenitor Cells to Differentiate 280
3. The Aged Skeletal Muscle Niche Impairs Normal Regeneration: TGF- beta 1 Signaling Maintains Satellite Cell Quiescence and Leads to Scar Tissue Formation 282
4. Toolbox to Combat TGF- beta 1-induced Aging of Satellite Cell Niche 285
5. Biomaterials to the Rescue: Proposed Strategies for Adult Skeletal Muscle Regeneration 287
5.1 Engineering an In Vitro Niche for Robust Skeletal Muscle Regeneration 287
5.1.1 Alignment of In Vitro Skeletal Muscle Fibers 289
5.1.2 Effects of Synthetic Niche Stiffness on Skeletal Muscle Regeneration 290
5.1.3 Electrical Stimulation of Tissue-engineered Skeletal Muscle 290
5.1.4 Vascularization of Tissue-engineered Skeletal Muscle 291
5.1.5 Natural Skeletal Muscle Niches: Mimicking the In Vivo Environment 292
5.2 Biomaterial Strategies to Combat Aging of the Muscle Stem Cell Niche 294
5.2.1 Gene and Drug Delivery Methods to Promote Skeletal Muscle Regeneration 294
5.2.2 Novel Targeting Strategies for TGF- beta 1 Inhibition 295
A biomaterial platform for regulating TGF- beta 1 levels to ‘young’ levels in the aged niche 295
5.3 Satellite Cells and Muscle Stem Cells: Biomaterials to Help Determine Who is Who 297
5.4 Use of Biomaterials in Tissue Engineering Applications 299
6. Conclusion 299
Acknowledgments 299
References 299
Author Index 311